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129Xe Gas-Exchange MRI in Pediatrics with Lung Disease

Matthew M. Willmering¹, Ziyi Wang², Hui Wang^1,3,4, Laura L. Walkup¹, Bastiaan Driehuys^2,5, Zackary I. Cleveland^1,4,6, and Jason C. Woods^1,4,6

¹Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Duke University, Durham, NC, United States, ³Philips, Cincinnati, OH, United States, ⁴University of Cincinnati, Cincinnati, OH, United States, ⁵Duke University Medical Center, Durham, NC, United States, ⁶University of Cincinnati Medical Center, Cincinnati, OH, United States

Synopsis

The solubility properties of hyperpolarized ¹²⁹Xe have made it attractive in many translational pulmonary imaging studies; the large chemical-shift range can be exploited to obtain semi-quantitative ventilation, barrier-uptake, and RBC-transfer images. To date, the technique has demonstrated significant changes in gas exchange in adult lung disease, but has yet to be explored in children, where pulmonary function testing can be more challenging (or impossible). This pediatric gap caused us to pursue ¹²⁹Xe gas-exchange MRI at the now-common field of 3T; here, we present the first demonstration of dissolved-phase xenon imaging in pediatrics (with cystic fibrosis and post-bone marrow transplant).

Purpose

¹²⁹Xe ventilation MRI correlates well with pulmonary function tests while being more sensitive to early disease, provides regional information, and been shown to be safe in pediatrics^1–7. However, xenon also diffuses into the lung barrier (interstitium and pleura) and ultimately into red blood cells (RBCs), which can be measured directly as a proxy for gas exchange. Each environment provides a different chemical shift (Figure 1). With hyperpolarized ¹²⁹Xe gas-exchange MRI, spatial mapping of barrier-uptake and RBC-transfer are possible and correlate with pulmonary diffusing capacity (DLCO) while providing regional information^8–16. Here, we implement this technique for the first time in pediatric patients.

Methods

A volume of ¹²⁹Xe (86% enriched; ≈1/6 total lung capacity, capped at 1L) was hyperpolarized to 30-40% via a Polarean 9820 xenon polarizer; but decayed to 15-25% by the time of imaging. A sequence based on that reported for 3T was implemented on a Philips 3T Acheiva¹⁵. A 3D-radial sequence (643 matrix, (380mm)³ FOV, 0.6ms readout duration, middle-lobe-sinc excitation, pulse length=0.63ms, TR=6.5ms, 15s breath-hold, 770 radial views) was implemented with 10 interleaves (sweeps from +k_z to -k_z). TE was optimized before each scan to determine the TE₉₀ (time for the barrier and RBC to be 90° out of phase, typically 0.48-0.52ms). Each k-space projection was repeated at three frequencies (each frequency with a different flip angle) before moving to the next trajectory; +7400Hz/15°, 0Hz/0.5°, and -7400Hz/15° (relative to gas-phase). Additionally, proton 3D-radial images (identical FOV/voxel, block pulse, 5° flip angle) were acquired for masking during an additional 15s breath-hold of air.

Five images (ventilation, gas phase, dissolved-phase, off-resonance, and proton) were reconstructed via Graphical Programming Interface into 128³ images¹⁷. Ventilation/proton images were reconstructed with a 128³-matrix kernel while the others used a 64³-matrix kernel for higher SNR. In Matlab, the dissolved-phase image was separated into barrier and RBC images via the 1-point Dixon technique¹³. Ventilation images were normalized via their 99th percentile⁵. RBC and barrier images were normalized by the gas image, correcting for different flip angles, to obtain barrier-uptake and RBC-transfer images¹⁴. The ventilation, barrier-uptake, and RBC-transfer images were binned according to a previously-reported healthy mean and standard deviation^5,14. Three subjects were imaged; 1) 12-year old female post-BMT without graft-vs-host (GVH) complications, 2) 15-year old male with cystic fibrosis, and 3) 25-year old female post-BMT with GVH complications of the lung.

Results

The resulting images had mean SNRs of 7.6±1.8, 27.6±6.9, 5.6±3.0, and 4.6±1.6 for high-resolution ventilation, low-resolution gas, barrier-uptake, and RBC-transfer, respectively. Binned maps are shown for the subjects (Figures 2, 3, and 4)¹⁴.

The post-BMT subject without GVH exhibited normal ventilation (1% complete-defect, 9% low-ventilation), a barrier-uptake of 0.0050±0.0013, an RBC-transfer of 0.0052±0.0014, and an RBC/barrier ratio of 1.1. The subject exhibits relatively homogeneous ventilation with few to no obstructive defects, indicative of healthy lungs.

The CF subject had impaired ventilation (11% complete-defect, 23% low-ventilation), a barrier-uptake of 0.0056±0.0017, an RBC-transfer of 0.0047±0.0021, and an RBC/barrier ratio of 1.0. The ventilation images exhibit defects in the right-lower lobe and apex of both lungs. The gas-exchange images have only minor deficit regions, indicative of minor gas-exchange impairment in ventilating regions (slightly increased barrier signal, decreased RBC signal, and corresponding decreased RBC/barrier ratio).

The post-BMT subject with GVH exhibited severely impaired ventilation (39% complete-defect, 28% low-ventilation), a barrier-uptake of 0.0043±0.0012, an RBC-transfer of 0.0034±0.0011, and an RBC/barrier ratio of 0.9. The ventilation defects affected most of the lung, barrier-uptake was moderately impaired, and RBC-transfer was severely diminished.

Discussion

The mean RBC-transfer is larger for all subjects when compared to previously-reported means at 1.5T¹⁴, though recently-published methods for 3T gas-exchange imaging also showed larger RBC-transfer¹⁵. Modifications of many parameters at 3T, including the use of smaller flip angles and longer TRs, would result in larger steady-state magnetization due to the decreased saturation of the dissolved-phase signals and longer time for the signals to diffuse from the gas and build-up in the barrier and RBCs. Thus, a distribution of gas-exchange MRI healthy subjects is necessary at 3T for quantitative comparison to those with gas-exchange-related lung disease.

Conclusion

Gas-exchange MRI with HP ¹²⁹Xe is possible in pediatrics with and without lung disease and provides additional regional measurements of pulmonary function. These results correspond well with previously-reported values in young adults. Additionally, the information provided via ¹²⁹Xe gas-exchange MRI allows for functional imaging of interstitial or RBC-abnormalities that may not have ventilation deficits. Lastly, the technique provides means to asses regional lung function in pediatrics where standard clinical pulmonary function tests can be challenging or impossible.

Acknowledgements

The authors thank the following sources for research funding and support: NIH R01 HL131012 and NIH R44 HL123299.

References

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4. He M, Robertson SH, Kaushik SS, et al. Dose and pulse sequence considerations for hyperpolarized 129Xe ventilation MRI. Magn Reson Imaging. 2015;33(7):877-885. doi:10.1016/j.mri.2015.04.005.

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6. Thomen RP, Walkup LL, Roach DJ, Cleveland ZI, Clancy JP, Woods JC. Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients. J Cyst Fibros. 2016. doi:http://dx.doi.org/10.1016/j.jcf.2016.07.008.

7. Walkup LL, Thomen RP, Akinyi TG, et al. Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Pediatr Radiol. 2016;46(12):1651-1662. doi:10.1007/s00247-016-3672-1.

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Figures

Figure 1: Example ¹²⁹Xe spectrum from the 15-year old male subject with cystic fibrosis. Black dots represent the acquired NMR magnitude spectrum, the grey line is the corresponding magnitude fit to the data. The red, blue, and green lines are the real components of the fits for ¹²⁹Xe in RBC, barrier, and gas, respectively, illustrating the phase of those components. 0 Hz corresponds to the xenon gas frequency.

Figure 2: Gas-exchange binned maps for the 12-year old post-BMT subject without GVH complications. Top row: ventilation binned map; middle row: barrier-uptake binned map: bottom row: RBC-transfer binned map. Corresponding bins for each row are found in the first slice. Red indicates defect, orange indicate low intensity, and the top two bins indicate high intensity.

Figure 3: Gas-exchange binned maps for the 15-year old cystic fibrosis subject. Top row: ventilation binned map; middle row: barrier-uptake binned map: bottom row: RBC-transfer binned map. Corresponding bins for each row are found in the first slice. Red indicates defect, orange indicate low intensity, and the top two bins indicate high intensity.

Figure 4: Gas-exchange binned maps for the 25-year old post-BMT subject with GVH complications. Top row: ventilation binned map; middle row: barrier-uptake binned map: bottom row: RBC-transfer binned map. Corresponding bins for each row are found in the first slice. Red indicates defect, orange indicate low intensity, and the top two bins indicate high intensity.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)

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